Multi-well arrays have long been popular for separately performing numerous chemical and/or biological reactions at substantially the same time. Perhaps the most popular multi-well format in recent years has been the 96-well microplate. Typically, several microliters of reagents are placed in each of the 96 reaction wells, per assay. In an effort to decrease reagent costs, as well as to increase throughput, many laboratory directors are now moving toward the use of even higher-density plates having very small wells, such as 384- and1536-well formats with wells about 1 millimeter in diameter, or smaller. With the higher density well formats, comes the need for distributing even smaller amounts of substances (e.g. <1 nL) into extremely compact arrays.
Most conventional automated micro-volume deposition systems dispense substances in fluid form, using robotic delivery assemblies. In a typical system, a robot aspirates fluid into one or more ejectors, moves a loaded ejector to a well in a micro-card or plate, and delivers an aliquot of fluid. Commonly used ejectors include “non-contact” devices, such as ink jet nozzles, and “contact” devices, such as a pens or quills. Ink jets, pens, and quills are well-known devices used in a variety of applications. Unfortunately, for the purpose of depositing numerous substances into the wells of a micro-card or plate, each of these devices is associated with certain disadvantages. For example, ink jets generally work fine when the fluid of interest has been carefully optimized for the nozzle. However, when depositing many different fluids through the same nozzle, optimization for each separate fluid is often impractical. As a result, the nozzles can become clogged. With regard to pens and quills, these devices can collide with the well walls, and are generally too slow for cost-effective operations.
The task of delivering micro-volumes of fluidic substances can be especially challenging when the substance deposited at each location is unique to one or only a few positions in the array. Further complications can arise when multiple fluidic substances are serially deposited into each well. For example, liquids can drip and splatter, contaminating reagents in neighboring wells. As another disadvantage, all devices contacting a fluid reagent must be cleaned, or disposed of, before being used with a different fluidic reagent. This is necessary to prevent mixing (i.e., contamination) of one reagent with another. It should be appreciated that multiple rounds of cleaning and aspiration can be time consuming and expensive, as well. This is especially true for applications requiring a large number of different substances. As a further disadvantage, it is often difficult to control the volume of fluid dispensed with a high degree of accuracy. Also, small amounts of dispensed liquid can be difficult to detect with standard imaging systems. Accordingly, dispensing errors can go undetected and, thus, uncorrected.
The need is apparent for an apparatus and process capable of fabricating an array of substances on a micro-card or plate in a relatively fast, efficient and accurate manner.